Gene/Protein Disease Symptom Drug Enzyme Compound
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Azathioprine is used in a variety of dermatological conditions. However, because of its side-effect profile, azathioprine is limited for use in patients with severe disease. An unpredictable, rare and potentially fatal side-effect of azathioprine is the development of a hypersensitivity reaction, often consisting of fever, hypotension and oliguria. We describe a 17-year-old patient with leucocytoclastic vasculitis who was placed on azathioprine; within 15 days of start of therapy, she developed a fever. Azathioprine was discontinued and an evaluation for sepsis was undertaken; all cultures were negative and the fever abated. Azathioprine was restarted 5 days later. After a single dose, fever, nausea and vomiting, diarrhoea, hypotension, tachycardia and oliguria developed and the patient was admitted to an intensive care unit. Azathioprine was discontinued and investigations revealed no sign of an infection. All the above signs and symptoms abated within 24 h and the patient was discharged from hospital in 7 days. A review of 28 case reports in the literature of azathioprine-induced hypersensitivity reactions suggest that most commonly a fever and gastrointestinal symptoms occurred on initial presentation. In addition, a maculopapular rash, urticaria, vasculitis, erythema multiforme or erythema nodosum may occur. Hepatotoxicity and nephritis have also been reported. The aetiology of the reaction is unknown but sudden onset of fever and hypotension suggests that this reaction may be due to cytokine or mediator release induced by azathioprine. As azathioprine is metabolized to 6-MP, rechallenges to both should be avoided in patients who experienced an azathioprine hypersensitivity-like reaction.
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PMID:Azathioprine hypersensitivity-like reactions--a case report and a review of the literature. 854

The probability of death in patients with acute renal failure (ARF) remains high. A valid prognostic index available on patient admission and during follow-up could be helpful for decision making. In this study, 94 ARF patients requiring dialysis (not responding to a previous single dose of furosemide 15 mg/kg) were included. On admission, patients were classified according to a Simplified Acute Physiology Score (SAPS) of < or = 15 or > 15. The prognostic value of 11 risk factors was analyzed. Only 6 in 11 risk factors were significant by univariate analysis: age (> 55 years) (0.02), mechanical ventilation (0.008), oliguria (< 500 mL/day during the first 5 days) (0.02), sepsis (0.001), shock (0.007), and serum bilirubin (> 30 mumol) (0.001). Only oliguria and sepsis were significant risk factors by multivariate analysis. Overall mortality rate was 41%. Mortality rate was higher in patients with SAPS > 15 (65%) than in those with SAPS < or = 15 (22%) (0.001). Patients with > 3 risk factors showed a significantly higher mortality rate than patients with < 3 risk factors (all patients disregarding SAPS) (0.001). Considering the worst combination of risk factors by univariate analysis, mortality prediction was 56% if oliguria, sepsis, and high serum bilirubin were present, and reached 80% if an older age was added (four risk factors). Ventilation increased probability of death to 92% (five risk factors). If all six risk factors were present, the probability rose to 96%. The corresponding observed mortality rate was 32% for three risk factors, 70% for four, 81% for five and 100% for six risk factors. The results suggest that probability of death in ARF requiring dialysis can be correctly estimated when more than three significant risk factors are present. If confirmed, they could avoid using a more complex severity scoring system in patients with ARF requiring dialysis.
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PMID:A simple prognostic index for patients with acute renal failure requiring dialysis. French Multicentric Prospective Study on Furosemide in Acute Renal Failure Requiring Dialysis. 887 83

In order to evaluate the role of underlying disease in the high mortality observed in acute renal failure (ARF) and risk factors related to the development of oliguric ARF in renal allograft recipients, two groups were selected: 34 patients with native kidneys, aged 16 and 57 years, and presenting ischemic ARF caused by cardiovascular collapse, with no signs of infection at the time of diagnosis; and 34 renal allograft recipients who developed ARF immediately after transplantation, without rejection. ARF was defined either as 30% increase of basal plasmatic creatinine in patients with native kidneys or nonnormalization of plasmatic creatinine at day 5 after transplantation in renal allograft recipients; oliguria as diuresis < or = 400 mL/24 h. There were no differences in age, male frequency, oliguria presence and duration, need for dialysis, and infection episodes for renal allograft recipients and patients with native kidneys. The development of sepsis (3% and 41%) and death rate (3% and 44%) were higher in patients with native kidneys (p < 0.01). The renal allograft recipients with both oliguric (n = 18) and nonoliguric (n = 16) ARF were evaluated and no difference was observed in the recipient's age, donor's age, cold ischemia time, time elapsed until plasmatic creatinine normalization, donor's plasmatic creatinine or urea, and mean arterial pressure. No differences were observed between the groups regarding frequency of infection episodes during ARF and frequency of death. In conclusion, renal allograft recipients presented a lower death rate and were less susceptible to sepsis. Cold ischemia time, age, and hemodynamic characteristics of the donor did not affect the development of oliguria.
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PMID:Acute renal failure in renal allograft recipients and patients with native kidneys. 910 1

Acute renal failure (ARF) in burn disease results in a range of phenomena important not only from theoretical, but also from practical point of views, whose causes are manifold. ARF is generally defined as a rapid renal failure resulting in accumulation of protein metabolism degradation products (catabolism). It has been known, for some time, that thermal agents do not produce only local skin damages, but also disturb the integrity of the whole organism producing major functional damages of all organs and systems. Most frequently organs affected by burn disease are the following: the lungs, the heart, the kidney, the liver and blood coagulation systems. There are many factors influencing the renal function during the burns. The most important are: decreased cardiac output, respiratory failure with hypoxia and acidosis, toxaemia and sepsis [1, 4, 6 7, 8-10, 12, 19]. ARF in burn disease may be early due to hypovolaemia and hypoperfusion of the kidneys or late, occurring after a week as a consequence of infection and endotoxaemia. Development of ARF in burn disease is a very unfavorable prognostic sign necessitating a complex evaluation. Anuria in an early phase of burn disease may indicate the development of ARF, particularly if urine findings are positive to haemoglobin, proteins, myoglobin, which is of the utmost importance in deep burns inflicted by high voltage current. The immediate cause of anuria in burn disease may be a reflex transfer and penetration of the large quantities of toxic materials into the circulation form the region affected by burns leading to the spasm of afferent glomerular arteriolae producing sudden discontinuation of glomerular filtration. After burns, sudden increase in the osmotic activity ensues in the affected tissue. Some low molecular links may result, and such particles tend to change the osmotic balance and stimulate the development of oedema, and if not excreted, they increase osmolarity. In 20-30% of the patients with burn disease anuria is absent [2, 5, 11, 14, 18, 20]. The genesis of burn disease-associated anaemias is therefore multifactorial. These factors are the following: haemorrhage, haemolysis and etrythropoiesis level decrease. In massive burns, large amounts of non-specific inflammatory components are produced as well: prostaglandins, histamine, quinines leukocyte phenomena, bacterial toxins, etc. [1, 6, 13-16]. The study based on a years-long treatment of our patients with burn disease included on 100 patients. The youngest of the patients was 14 years old, and the oldest 65 years. The percent of burns-affected body surface ranged from 25% to 75%. In 3/4 of the patients the picture of an early renal failure developed, with oliguria immediately after infliction of the burns with rapid increase of serum urea and creatinine levels, while in 1/4 of the patients ARF occurred on the eighth day following the infliction of the burns. "late form of acute renal failure". Among our series with burn disease, anuria was present in 34.0% of patients and oliguria in 25.0%. ARF (early phase) occurred in 59 patients, 38 patients had no sing of ARF, while late ARF developed only in 3 patients. ARF-associated mortality rate was high among these patients (23%), being 6% among anuric patients with ARF and 17% in patients with ARF with anuria. Seventy-seven percent of the patients survived, and their serum and urine analyses performed upon subsequent out-patient follow-up examinations ranged within normal values. Such high percentage of survival among our patients included in the study is based on an early diagnosis of ARF, understanding of pathophysiology of shock associated with burn disease, adequate therapeutic approaches, including both medicamentous treatment and extracorporeal haemodialysis along with early surgical management (Shema 1, 2). For the time being, haemodialysis is the most effective therapeutical procedure in the treatment of ARF, although the mortality rate of dialyzable patients
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PMID:[Acute renal insufficiency caused by burn injury]. 910 56

The purpose of this prospective study was to determine whether the course and prognosis of acute renal failure (ARF) in patients with and without sepsis are different. Two hundred fifty-two (8%) of 3086 consecutive patients admitted to a medical-surgical intensive care unit (ICU) developed ARE. One hundred forty-nine (59%) were septic and 103 (41%) were non-septic. No differences were found between groups regarding the incidence of oliguria, hyperkalemia, hypercatabolism, gastrointestinal bleeding, duration of oligria and renal deficit, severity of axotemia, dialysis requirements and duration of stay in the hospital. There were statistically significant differences between septic and non septic patients with respect of hyponatremia (67.8 vs 54.4%, p < 0.04), respiratory failure (68 vs 54%, p < 0.04), and thrombocytopenia (64 vs 48%, p < 0.02). Mortality in septic patients was higher than in non-septics (56 vs 42.7%, p < 0.009). Factors associated with increased mortality in ARF septic patients were respiratory failure, metabolic acidosis and oliguria while in the non-septics they were hepatic dysfunction, hyperkalemia, respiratory failure and infection acquired during the course of renal failure. We conclude that ARF developing in septic patients has a higher mortality than that of non-septic patients, whereas the incidence of hypercatabolism and oliguria was not different between both groups.
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PMID:[Acute kidney failure in patients with and without sepsis: prognosis and clinical course]. 919 93

The changing trend of today's ARF in Thailand had led to requirement of epidemiologic data for management and planning. Retrospective review of adult inpatient records for 5 years of Ramathibodi Hospital was performed. Normal initial serum creatinine rising to double its value within one week and/or oliguria were the inclusion criteria. Data from another 3 university hospitals were used for comparison. AFR is the second most common renal disease at Ramathibodi Hospital with sepsis as the major underlying etiology. Among 396 cases of ARF, 194 were non-oliguric, 150 oliguric and 52 anuric. Non-oliguric cases needed lesser dialysis and had lower mortality. The number of AFR patients from 4 university hospitals varied from 0.14 to 0.18 per cent of hospital admission. If we consider the incidence of AFR in general hospital admission to be 0.1 per cent and the average hospital admission/year of Thailand was 3.25 million, there will be 3,250 cases/year or 55 cases/million/population year. If 4 dialyses/case was considered, 220 dialyses/ year/million population was required. We suggested that the hospitals of the province with population above 1 million should have a hemodialysis unit for both their local service and referral cases and all provincial hospitals should develop at least a peritoneal dialysis facility for increasing cases in ARF.
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PMID:Acute renal failure (ARF) in Thailand. Retrospective analysis in a medical center. 927 69

In 1989-1995 229 patients with acute renal failure were treated by hemodialysis. A total of 1470 procedures have been performed, 8.8 +/- 1.5, on the average. 61 patients (26.6%) died. There is no significant relation between duration of oliguria, maximum BUN, creatinine level and lethality. The latter is associated with the patient's age, acute respiratory failure, sepsis, coma, hyperbilirubinemia and hypoproteinemia. Lethality was higher at failure of two and more organs and poor prognosis defined by a simplified acute physiology score (SAPS). 10 patients (5.9%) were discharged with increased creatinine level. Conventional hemodialysis is recommended as a basic technique of dialysis for patients with mono-organ failure and relatively good prognosis according to SAPS scale.
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PMID:[The course and outcome of acute kidney failure in patients treated by hemodialysis]. 929 76

We studied 28 consecutive patients (18 males and 10 females), 1-32 years of age, admitted to the intensive care unit from January 1989 to July 1995, with acute renal failure (ARF) due to meningococcal septicemia. All patients were treated with dexamethasone, penicillin, and/or chloramphenicol. Twenty-two patients presented septic shock and needed fluid replacement and vasoactive drugs. Acute renal failure was oliguric in 67.8%. Maximum levels of blood urea and serum creatinine were 210.3 +/- 26.6 mg/dL and 6.9 +/- 1.3 mg/dL, respectively. Metabolic acidosis was observed in 89.3% and hyperkalemia in 43%. The fractional excretion of sodium on day 1 was high (9.9 +/- 0.6%). The urinalysis did not show trace protein, but hematuria was positive in 81%. The mortality rate was 63.3%. In the 10 survivors, oliguria was present for a period of 12.7 +/- 2.4 days, and the period to reach a normal serum creatinine level was 20.2 +/- 4.7 days, although in two female patients, 7 and 17 years old, the elevated serum creatinine persisted. Renal biopsy was performed in one of these patients which revealed bilateral cortical necrosis. These data show that acute renal failure in meningococcemia presents high mortality rate associated to shock; 80% of the survivors recover renal function; and bilateral cortical necrosis occurred in one patient in this series.
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PMID:Outcome of acute renal failure in meningococcemia. 941 38

Prophylactic hemodialysis has been employed in the treatment of 15 patients with acute renal failure due to acute tubular necrosis (12), bilateral renal cortical necrosis (two), and poststreptococcal glomerulonephritis (one). Dialyses, usually lasting six hours each, were begun before clinical evidence of uremia developed in each patient and/or before the nonprotein nitrogen reached 200 mg.%, and were repeated daily or often enough to maintain the nonprotein nitrogen below 150 mg.%. The hypothesis underlying this technic postulates (1) that wasting, sepsis and impaired wound healing in these patients may reflect tissue injury by the same dialyzable toxic agents which produce the uremic symptoms that are readily reversible by dialysis, and (2) that repeated dialyses should therefore prevent both clinical uremia and the later, often lethal sequelae. The results contrast dramatically with our own past experience in treating patients with acute renal failure with a carefully executed medical regimen together with hemodialysis on conventional indications. Except in one instance of crush injury with progressive intracerebral damage, and one brief occasion in another individual, these patients experienced a stable, convalescent clinical course, remained free of uremic symptoms or chemical imbalances, ate at least three meals daily which were unrestricted in amount and composition, and were ambulatory between dialyses unless confined to bed by associated disease. Wounds healed well. Infection either did not occur, or subsided after appropriate therapy. Fluid restriction was liberalized by means of ultrafiltration with dialysis. Regional heparinization of only the extracorporeal circuit eliminated actual or impending bleeding as a contraindication to dialysis. Chronic vessel cannulation made the frequent dialyses possible, but may have provided the route for repeated, transient bacterial contamination of the blood stream in the first hour of many dialyses. Marked anemia, despite reticulocytosis, moderate to mild weight loss and some mental deficit persisted in spite of the general clinical improvement and well-being. Three patients with tubular necrosis died after seven, 11 and 26 days of oliguria; both patients with bilateral renal cortical necrosis also succumbed, on the seventy-third and ninety-second days of renal failure, and after 29 and 40 dialyses, respectively. At autopsy, evidence of sepsis was conspicuously absent. The remaining 10 patients survived. Thus some, but not all, clinical manifestations of acute renal failure appear to be favorably influenced by prophylactic dialysis treatment. Our initial experience in this group of 15 patients does not of course prove that freedom from complications and a significantly better outlook for survival can be assured to patients with acute renal failure by these methods. However, it seems to offer a reasonable hope of this possibility which we cannot attach to management by medical measures alone, or by dialysis on conventional indications. If this hope is realized in greatly extended, subsequent series, then it seems inevitable that some form of prophylactic dialysis, or some equally effective alternative, should be adopted in treating the majority of patients with acute renal failure.
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PMID:Prophylactic hemodialysis in the treatment of acute renal failure. Annals of Internal Medicine, 53:992-1016, 1960. 984 96

We report the case of a 21-year-old man who had been developing acute renal failure with Methicillin-resistant Staphylococcus aureus (MRSA) colitis and sepsis. He was admitted for consciousness disturbance, nausea, vomiting, and diarrhea. Oliguria was also observed and his serum creatinine level was elevated to 10 mg/dl. Urinary protein was positive and an abundance of hyaline cast were seen in urinary sedimentation. Diarrhea and pyrexia were prolonged and serum C-reactive proteins were elevated, but lymphocyte and leukocyte counts temporarily decreased from the 3rd to the 6th hospital day and remained low until normalizing after the 14th day. His clinical symptoms improved with hemodialysis (HD) and effective antibiotic therapies. An MRSA strain producing toxic shock syndrome toxin-1 (TSST-1), a super antigen which specifically stimulates human V beta 2-positive T cells, was separated from his feces and blood. To ascertain the cause of his renal dysfunction, a renal biopsy was performed on the 8th day. His renal histology revealed acute interstitial nephritis with severe inflammatory cell infiltration around the medullary areas without glomerular changes. Most of the infiltrated cells were small monocytes, and lymphoid cells were rich in the interstitium. With immunohistochemical staining, over 70% of T-cells were V beta 2-positive. TSST-1-producing MRSA was detected in his blood specimen. Furthermore, V beta 2-positive T cells were accumulated in the renal intersititium, and transient lymphocytopenia was observed. These data suggested the following possible pathogenesis for interstitial nephritis: TSST-1 acts as a super antigen in the renal interstitium where major histocompatibility complex (MHC) is class-2-positive, thereby resulting in interstitial nephritis with T cell migration.
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PMID:[A case of interstitial nephritis induced by a super antigen produced by methicillin-resistant Staphylococcus aureus (MRSA) presenting as acute renal failure]. 1036 25


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